Vitamin A: Two polar metabolites of retinoic acid found in bile will be isolated in pure form and characterized chemically. Th isolation of other biliary metabolites of retinoic acid will be examined. New methods assaying biological activity of metabolites will be developed. Vitamin D: Continued emphasis will be placed on the chemical synthesis of vitamin D analogs, in particular, 25-methylvitamin D3, 1,25-difluorovitamin D3, and 25-difluoro, 25-hydroxyvitamin D and 25-difluoro,1,25-dihydroxyvitamin D3 will be synthesized. Considerable effort will be placed on the isolation and identification of new metabolites of vitamin D. Work will continue on the solubilization of the vitamin D hydroxylases, the separation of their components and their reconstitution. Vitamin K: Attempts will continue in the purification of the vitamin K-dependent carboxylase. The mechanism of carboxylation reaction will continue with the use of oxygen-18 to determine if a vitamin K hydroperoxide radical is an intermediate. Vitamin E: Studies emphasizing "oxygen stessor" effects of anticancer drugs such as adriamycine and anthracycline analogs in relation to vitamin E and selenium will continue. Studies on glutathione peroxidase synthesis in vitro will continue especially selenium incorporation. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.